The Efficacy of 10-day and 14-day Bismuth-based Quadruple Therapy in First-line H. Pylori Eradication

NCT04527055 | Enrolling By Invitation Phase 4

• 1 other identifier: B-BR-109-012
• Study Type: interventional
• Target: 312
• Locations: 1 country
• Sites: 1

Brief Summary

Helicobacter pylori (H. pylori) infection is the major cause of gastritis, peptic ulcer disease, and gastric cancer in adults. Bismuth-based quadruple therapy is recommended by a recent review to be the first-line treatment for H. pylori eradication, replacing clarithromycin-based triple therapy. It is because the eradication rates of triple therapy in adults have declined due to increasing clarithromycin resistance. The best regimen for H. pylori eradication should be the one which succeeds on the first attempt. However, the effectiveness and the optimal duration of bismuth-based quadruple therapy for first-line H. pylori eradication in adults are unknown. Moreover, the impacts on gut microbiota after H. pylori eradication should be concerned; for example, bismuth-based quadruple therapy decreases F. prausnitzii richness. The transient perturbation of the gut microbiota after H. pylori eradication were restored at 8 weeks and one year in subjects receiving clarithromycin-based triple therapy but not fully recovered in those receiving bismuth-based quadruple therapy. Therefore, the important issues are that the short-term and long-term gut dysbiosis and the recovery of gut F. prausnitzii depletion in H. pylori-infected adult patients after bismuth-based quadruple therapy. It is also uncertain the role of irreversible gut dysbiosis even though H. pylori is eradicated in gastric persist inflammation and progress to cancer, and whether probiotics could be helpful in recovering gut dysbiosis. The therapeutic strategy to eradicate H. pylori infection is based on antibiotics; however, this strategy not only increases drug resistant rates of the pathogen but also shapes the gut microbiota. The investigators hypothesize that bismuth-based quadruple therapy could be an optimal regimen for first-line H. pylori eradication in the era of increasing clarithromycin resistance; moreover, gut dysbiosis could be reversed after bismuth-based quadruple therapy. Furthermore, the efficacy of the10-day course is not inferior to that of the 14-day course in H. pylori eradication. The investigators also hypothesize that probiotics could restore gastric or gut dysbiosis, especially gut F. prausnitzii depletion.

Conditions

Helicobacter Pylori Infection; Dysbiosis; Probiotics

Outcome Measures

Primary Outcomes (1)

• The successful eradication rate

  The patients stop taking the proton pump inhibitor and antibiotics for 4 to 6 weeks, and then they receive 13C-UBT or an H. pylori stool antigen test to confirm successful eradication or not.

  About 4 to 6 weeks after receiving the H. pylori eradication regimen

Secondary Outcomes (5)

• Adverse effects and adherence to medications of the 10-day bismuth-based quadruple therapy and 14-day bismuth-based quadruple therapy groups

  About 2 to 4 weeks after receiving the H. pylori eradication regimen

• Fecal microbiota and metabolites and the microbial evolution after H. pylori eradication

  Baseline, 6-12 months after receiving the H. pylori eradication regimen or after endoscopy

• Fecal inflammatory parameters and their evolution after H. pylori eradication

  Baseline, 2, 6, 9, and 12 months after receiving the H. pylori eradication regimen or after endoscopy

• Gastric microbiota and its evolution after H. pylori eradication

  The patients receive surveillance endoscopy one year after H. pylori eradication

• Gastric precancerous conditions and the evolution after H. pylori eradication

  About 12 months after H. pylori eradication

Study Arms (5)

The 14-day bismuth-based quadruple therapy group

ACTIVE COMPARATOR

The patients receive a 14-day course of the bismuth-based quadruple therapy, including esomeprazole (Nexium 40 mg) 1 tab twice a day, bismuth subcitrate (dibismuth trioxide) (KCB F.C. 120 mg) 1 tab four times a day, metronidazole (Flagyl 250 mg) 2 tab thrice a day, and tetracycline (250 mg) 2 tab four times a day.

Drug: Bismuth Subcitrate 120 MG Oral Tablet; Drug: Esomeprazole 40mg; Drug: Metronidazole 250 MG; Drug: Tetracycline Pill

The 10-day bismuth-based quadruple therapy group

ACTIVE COMPARATOR

The patients receive a 10-day course of the bismuth-based quadruple therapy, including esomeprazole (Nexium 40 mg) 1 tab twice a day, bismuth subcitrate (dibismuth trioxide) (KCB F.C. 120 mg) 1 tab four times a day, metronidazole (Flagyl 250 mg) 2 tab thrice a day, and tetracycline (250 mg) 2 tab four times a day.

Drug: Bismuth Subcitrate 120 MG Oral Tablet; Drug: Esomeprazole 40mg; Drug: Metronidazole 250 MG; Drug: Tetracycline Pill

The non-H. pylori-infected control

NO INTERVENTION

Age- and sex-matched patients who do not have H. pylori infection by endoscopic gastric biopsy are enrolled as the non-H. pylori-infected control.

The probiotic therapy group

ACTIVE COMPARATOR

The patients who still have depletion of gut F. prausnitzii 12 months after H. pylori eradication are enrolled into the probiotic supplement trial. They are randomized to the probiotic therapy group ingesting probiotic powder twice daily for 24 weeks. The probiotic powder is named as "President AB powder", which contains an approximately equal mixture of Lactobacillus acidophilus and Bifidobacterium lactis Bb12 at a concentration of \>= 10E9 CFU/mL (President Corp., Tainan, Taiwan).

Dietary Supplement: Lactobacillus acidophilus and Bifidobacterium lactis Bb12

The non-probiotic control group

NO INTERVENTION

The patients who still have depletion of gut F. prausnitzii 12 months after H. pylori eradication are enrolled into the probiotic supplement trial. They are randomized to the non-probiotic control therapy and they do not ingest probiotic powder.

Interventions

Bismuth Subcitrate 120 MG Oral Tablet DRUG

Bismuth Subcitrate (120 MG Oral Tablet) 1 tab per oral four times per day for 14 days in the14-day bismuth-based quadruple therapy and for 10 days in the10-day bismuth-based quadruple therapy

Also known as: KCB F.C.

The 10-day bismuth-based quadruple therapy group; The 14-day bismuth-based quadruple therapy group

Lactobacillus acidophilus and Bifidobacterium lactis Bb12 DIETARY_SUPPLEMENT

The probiotic powder per oral twice daily for 24 weeks. The probiotic powder is named as "President AB powder", which contains an approximately equal mixture of Lactobacillus acidophilus and Bifidobacterium lactis Bb12 at a concentration of \>= 10E9 CFU/mL (President Corp., Tainan, Taiwan).

Also known as: President AB powder

The probiotic therapy group

Esomeprazole 40mg DRUG

Esomeprazole (40 mg) 1 tab per oral twice per day for 14 days in the14-day bismuth-based quadruple therapy and for 10 days in the10-day bismuth-based quadruple therapy

Also known as: Nexium

The 10-day bismuth-based quadruple therapy group; The 14-day bismuth-based quadruple therapy group

Metronidazole 250 MG DRUG

Metronidazole (250 MG) 2 tab per oral thrice per day for 14 days in the14-day bismuth-based quadruple therapy and for 10 days in the10-day bismuth-based quadruple therapy

Also known as: Tolizole

The 10-day bismuth-based quadruple therapy group; The 14-day bismuth-based quadruple therapy group

Tetracycline Pill DRUG

Tetracycline (250 MG) 2 tab per oral four times per day for 14 days in the14-day bismuth-based quadruple therapy and for 10 days in the10-day bismuth-based quadruple therapy

Also known as: Tetracycline (250 mg)

The 10-day bismuth-based quadruple therapy group; The 14-day bismuth-based quadruple therapy group

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who are \> 18 years
• Receive gastroscopy because of dyspepsia, acid regurgitation, melena, hematemesis, or others

You may not qualify if:

• Bleeding diathesis,
• Major organic diseases
• Malignancy
• Diseases treated with chemotherapy within one month
• Diseases treated with steroids within one month
• Diseases treated with antibiotics within one month,
• Users of aspirin within four weeks before enrollment
• Users of nonsteroidal anti-inflammatory drugs within four weeks before enrollment
• Users of cyclooxygenase-2 selective inhibitors within four weeks before enrollment
• History of H. pylori eradication
• Ingest probiotics or probiotics-containing yogurt with a frequency of \>= twice per week one month prior to enrollment

Sponsors & Collaborators

• National Cheng-Kung University Hospital: lead

Study Sites (1)

Helicobacter pylori study group, National Cheng Kung University Hospital

Tainan, 704302, Taiwan

Location

Related Publications (2)

• Yang EH, Chen WY, Chiang HC, Li CH, Wu IH, Chen PJ, Wu CT, Tsai YC, Cheng WC, Huang CJ, Sheu BS, Cheng HC. 10-Day versus 14-day bismuth quadruple therapy for first-line eradication of Helicobacter pylori infection: a randomised, open-label, non-inferiority trial. EClinicalMedicine. 2024 Mar 11;70:102529. doi: 10.1016/j.eclinm.2024.102529. eCollection 2024 Apr.

  PMID: 38500841 DERIVED

• Cheng HC, Yang YJ, Yang HB, Tsai YC, Chang WL, Wu CT, Kuo HY, Yu YT, Yang EH, Cheng WC, Chen WY, Sheu BS. Evolution of the Correa's cascade steps: A long-term endoscopic surveillance among non-ulcer dyspepsia and gastric ulcer after H. pylori eradication. J Formos Med Assoc. 2023 May;122(5):400-410. doi: 10.1016/j.jfma.2022.11.008. Epub 2022 Nov 30.

  PMID: 36463082 DERIVED

MeSH Terms

Conditions

Dysbiosis

Interventions

bismuth tripotassium dicitrate; Tablets; Lacteol; Esomeprazole; Metronidazole; Tetracycline

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations; Omeprazole; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nitroimidazoles; Nitro Compounds; Imidazoles; Azoles; Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Hsiu-Chi Cheng, PhD

  National Cheng-Kung University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Among the H. pylori-infected patients, they are randomized to the 14-day bismuth-based quadruple therapy group and the 10-day bismuth-based quadruple therapy group to receive a 14-day and 10-day course, respectively, of the bismuth-based quadruple therapy. Afterward, the patients stop taking the proton pump inhibitor and antibiotics for 4 to 6 weeks, and then they receive 13C-UBT or an H. pylori stool antigen test to confirm successful eradication or not. Patients' fecal microbiota profiling is performed before and after H. pylori eradication. If patients have the depletion of gut F. prausnitzii 12 months after H. pylori eradication, they are enrolled to the probiotic supplement trial. They are randomized to the probiotic therapy group ingesting probiotic powder twice daily for 24 weeks and the non-probiotic control group, respectively.

Study Record Dates

• First Submitted: August 21, 2020
• First Posted: August 26, 2020
• Study Start: May 6, 2020
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2028
• Last Updated: June 24, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)